An improved method for the measurement of superoxide dismutase (SOD) activity in guinea pig erythrocytes was developed. Alteration of guinea pig erythrocyte superoxide dismutase activity by the dietary antioxidants ascorbic acid and selenium was investigated. Erythrocyte SOD activity was directly related to the ascorbic acid intake of guinea pigs fed 0.05 ppm of selenium. Dietary levels of ascorbic acid were 0, 200 and 400 mg/kg). In guinea pigs fed 0.20 ppm of selenium, there was an increase in superoxide dismutase activity only in the group of animals fed the 400 mg ascorbic acid/kg of diet. Results suggest that substantial protection from deleterious O2-. can be provided by changes in dietary ascorbic acid.